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Antiepileptic drug treatment after temporal lobe epilepsy surgery: a randomized study comparing carbamazepine and polytherapy.

Temporal lobectomy is an effective treatment in selected patients with medically intractable temporal lobe epilepsy (TLE). Postoperative antiepileptic drug (AED) treatment guidelines have not been established, and patients are often treated with polytherapy postoperatively. We prospectively randomized 40 patients undergoing temporal lobectomy to monotherapy with carbamazepine (CBZ, 20) or to continuation of their presurgical polytherapy (20) to assess the efficacy and safety of each regimen during the first year after operation. No significant differences between groups were noted with respect to seizure recurrence rate and type or time of recurrence. Patients in the polytherapy group had a 30% incidence of drug-related side effects as compared with only 10% in the CBZ group. These results suggest that after temporal lobectomy for intractable epilepsy, patients can be safely treated with CBZ monotherapy and that treatment with multiple AEDs is not necessary.

Adolescent↗

Prognostic significance of ictal and interictal epileptiform activity in temporal lobe epilepsy.

Long-term electrocorticograms (ECoG), recorded by chronically implanted subdural electrodes during preoperative evaluation of 59 patients with temporal lobe epilepsy (TLE) were analyzed retrospectively to assess the prognostic relevance of distribution of interictal epileptiform potentials (IEP) and seizure origin (SO) and to investigate factors affecting their lateralization. Subsequent to preoperative evaluation, a standardized two thirds anterotemporal lobectomy including subtotal hippocampectomy had been performed in all patients. The following results were obtained: (a) Only patients with 100% lateralization of SO and IEP had excellent seizure outcome (= 89% seizure-free); (b) patients with bitemporal SO were unlikely to benefit from surgical treatment (= 12.5% seizure-free); (c) 40-56% patients with unilateral temporal SO and bitemporal IEP, became seizure-free irrespective of the degree of lateralization of IEP; and (d) multidimensional analysis of variance showed that lateralization of SO, presence of a magnetic resonance imaging (MRI)-detectable lesion, presence of hippocampal sclerosis, presence of febrile seizures and seizures at age < or = 6 years are the five most important variables indicating abolition of seizures. Combined analysis of ECoG-recorded SO and IEP allows prediction of postoperative seizure control within close boundaries.

Adolescent↗

Ontogeny of feline temporal lobe epilepsy. III: Spontaneous sleep and arousal disorders in amygdala-kindled kittens.

We report the ontogeny and persistence of sleep and arousal disorders in amygdala-kindled kittens. We also identify procedural differences that may explain discrepancies in the literature on postkindling sleep disorders. The study population consisted of 12 preadolescent kittens kindled between 2.5 and 6.5 months of age, 8 of which were followed to adulthood (> or = 1 year), and 8 unkindled implanted control animals. Sleep and seizure patterns were monitored on 12-24-h polygraphic or split-screen video recordings of EEG and behavioral activity. Kindled kittens displayed spontaneous seizure and interictal sleep anomalies that persisted to adulthood, as follows. As compared with neurosurgical controls, kindled kittens exhibited slow-wave sleep (SWS) and REM sleep insomnia at least 1 year after kindling and 1-5 months after convulsions, regardless of postictal recording delay. Sleep and arousal defects in kindled kittens were similar to but more pronounced than those in kindled adult cats, possibly because kittens spontaneously became epileptic. Detection of postkindling SWS insomnia could be masked by brief scoring epochs (less than the preferred 1-min epoch for cats); recurrent behavioral arousals after kindling frequently aborted 1-min SWS epochs but often did not interrupt 30-s SWS epochs (based on 1-min vs. 30-s minimum duration scoring criteria). Detection of postkindling REM sleep insomnia could be masked in kittens with alternating patterns of REM loss and REM rebound; all these kittens showed periodic bouts of REM onset from waking after kindling. Different data collection and analysis procedures influence detection of sleep and arousal disorders in amygdala-kindled cats when replication of findings is attempted. We conclude that these differences explain some controversies regarding the nature and prevalence of sleep disturbances in the kindling literature in temporal lobe epilepsy (TLE).

Amygdala↗

Prognostic value of qualitative magnetic resonance imaging hippocampal abnormalities in patients undergoing temporal lobectomy for medically refractory seizures.

In patients with temporal lobe epilepsy (TLE), high-resolution, magnetic resonance imaging (MRI) frequently demonstrates hippocampal atrophy and increased hippocampal signal. To assess the prognostic value of these findings, we studied 51 patients evaluated prospectively by a radiologist blinded to other preoperative evaluations. Thirty-one of 51 (61%) patients undergoing temporal lobectomy had visually apparent hippocampal atrophy or increased hippocampal signal on MRI (25 ipsilateral 3 contralateral, and 3 bilateral to the operated site). Patients with ipsilateral abnormalities became seizure-free more frequently than patients with normal scans [24 of 25 (96%) vs. 10 of 20 (50%) p < 0.015]. Both ipsilateral hippocampal atrophy and ipsilateral increased hippocampal signal independently predicted a seizure-free outcome. Qualitative MRI provides important prognostic information in patients undergoing temporal lobectomy.

Atrophy↗

Differentiation of temporal lobe ictal behavior associated with hippocampal sclerosis and tumors of temporal lobe.

Ictal behavioral characteristics may reflect seizure spread patterns and provide a clue to seizure onset location, between or within specific cerebral lobes. Sequential symptomatology might therefore distinguish patients with hippocampal sclerosis from patients with temporal lobe tumors. To determine ictal behavioral differences in patients of these groups, we analyzed 145 seizures of 33 patients with hippocampal sclerosis (group I) and 79 seizures of 22 patients with temporal lobe tumors (group II). First appearance of a variety of ictal behavioral characteristics was determined in three phases (first 5 s, 5-60 s, and from 60 s to mental clearing) for patients in both groups. Ipsilateral hand automatisms were significantly more frequent in the first 60 s in group I (p < 0.005). Onset of contralateral head turning was observed in the first 5 s only in group II (p < 0.05). First appearance of leg automatisms in group I and of oral automatisms in group II were very rare in phase 2 (p < 0.01, p < 0.005). Time of onset of other ictal behavioral characteristics and duration of seizures were not statistically different between the two groups. Ictal behavioral characteristics varied among and within patients and patient groups, but certain behavioral characteristics were helpful in differentiating these two groups of temporal lobe epilepsy (TLE) patients.

Adolescent↗

Serial cognitive testing in temporal lobe epilepsy: longitudinal changes with medical and surgical therapies.

Cognitive testing was repeated at intervals ranging from 1 to 8 years in 47 adult patients with temporal lobe epilepsy (TLE). Each patient underwent standardized batteries, including the Wechsler Adult Intelligence Scale, Revised (WAIS-R), and Wechsler Memory Scale (WMS). Both surgically treated and nonsurgical patients were examined. The nonsurgical group underwent serial testing for clinical indications, usually for complaints of memory dysfunction. Longitudinal testing could not verify any mean deterioration of intellect or memory in this group; variance over time was similar to test-retest norms in healthy controls. WAIS-R scores before and after resection in the surgical group were similar to our serial WAIS-R data in nonsurgical patients. When we divided surgical patients according to side of epileptogenesis, we noted the expected differences in verbal and visual memory. Right-sided surgery patients improved significantly in Full-Scale IQ (FSIQ) and tended to improve in logical memory on postoperative testing. Patients undergoing left resections had no retest improvement and tended to show decrease in several measures of verbal memory. Our findings should stimulate continued investigation into the natural history of lateralized memory and intellectual function in epilepsy, particularly to clarify long-term cognitive outcome in nonsurgical patients.

Adult↗

Differentiating clinical features of right and left temporal lobe seizures.

We reviewed 127 seizures in 19 consecutive patients with temporal lobe epilepsy (TLE) documented by EEG/closed-circuit TV (EEG-CCTV) monitoring. Ten patients had seizure onset in the right temporal lobe (RTL, 54 seizures), and 9 had seizure onset in the left temporal lobe (LTL, 73 seizures). We compared the clinical characteristics in the two groups and analyzed the seizures for frequency of auras, seizures secondarily generalized, automatisms, tonic head deviation, focal posturing and jerking, ictal speech, and postical manifestations. Automatisms overall were more common in the RTL group, but individual categories (extremity, head and trunk, oroalimentary) were comparable among the two groups. Contralateral focal jerking and tonic head deviation were more common in LTL lobe seizures, as were secondarily generalized seizures. In addition to focal motor symptoms, three features were most statistically significant in distinguishing the two groups: Postictal aphasia occurred exclusively in the LTL group, whereas well-formed ictal speech and rapid return to baseline postictally were noted only in RTL seizures.

Adolescent↗

Association of ipsilateral head turning and dystonia in temporal lobe seizures.

We evaluated head turning in 239 complex partial seizures (CPS) with or without generalization in 32 patients with unilateral temporal lobe epilepsy (TLE). Head turns occurred in 187 seizures of 31 patients, more than once in 71 seizures. The first head turn was ipsilateral to the focus in 162 seizures (87%), with a mean latency of 22 s, as compared with 83 s for contralateral first head turns. Concomitant dystonic posturing of the arm occurred with 71% of all ipsilateral head turns and with 16% of all contralateral head turns. The mean difference in absolute latency between the first head turn and concomitant dystonic posturing was 6 s. Examination of all instances of concomitant head turning and dystonic posturing (160) showed them to be contralateral to each other in 154 (96%). Furthermore, the dystonia was contralateral and head turning was ipsilateral to the focus in 149 (93%). Forty-one seizures secondarily generalized, with transitional tonic head deviation contralateral to the focus in 35. Early head turning suggests an ipsilateral temporal seizures focus, particularly when associated with contralateral dystonic posturing. Similar mechanisms may account for both. Tonic head deviation preceding secondary generalization probably has a different mechanism.

Adolescent↗

Language before and after temporal lobectomy: specificity of acute changes and relation to early risk factors.

We evaluated language functions in 154 patients with left hemisphere speech dominance undergoing anterior temporal lobectomy (ATL). Measures of phonemic and semantic fluency, confrontation naming, repetition, comprehension, and reading were administered before and 3 weeks postoperatively. Patients were grouped by focus (left, LT; right, RT) and presence of early risk factors for development of seizures (ER, early risk, < or = 5 years; NER, no early risk): (LT-ER, n = 45; RT-ER, n = 49; LT-NER, n = 27; RT-NER, n = 33). Preoperatively, the LT group showed a selective naming deficit as compared with the RT group. Postoperatively only the LT-NER group showed significant overall decline in language. For this group, the change was attributable to a selective decline in naming as compared with other functions. These data indicate that there is a specific risk to naming after dominant ATL for adult temporal lobe epilepsy (TLE) patients with a left hemisphere focus and the absence of an early risk factor for the development of seizures.

Aphasia↗

Is interictal temporal hypometabolism related to mesial temporal sclerosis? A positron emission tomography/magnetic resonance imaging confrontation.

The mechanism of interictal glucose hypometabolism remains unclear, but this abnormality occurs more frequently in temporal lobe epilepsy (TLE) than in other types of partial epilepsy. Therefore temporal hypometabolism has been suggested to reflect mesial temporal sclerosis (MTS). To investigate this, we selected 22 patients with refractory partial epilepsy of mesial temporal lobe origin (MTLE) who had hippocampal atrophy based on magnetic resonance imaging (MRI) volumetric analysis. We then analyzed the metabolic correlates of unilateral hippocampal atrophy. Thirteen temporal regions of interest (ROI) were defined on MRI scans for each individual and then applied to high-resolution FDG-positron emission tomography (PET) images obtained parallel to the long axis of the hippocampus. The most hypometabolic regions were the temporal pole and the hippocampal region. When we analyzed ensembles of temporal regions grouped into related networks, the temporolimbic network, which included the hippocampal region and the temporal pole, was abnormal in 95% of the patients at a 3-SD threshold. PET hypometabolism was highly correlated with the degree of hippocampal atrophy in this network, but not in other parts of the temporal lobe, which were less frequently hypometabolic. These data indicate that hypometabolism is a consequence of MTS in the temporolimbic region but not necessarily in the other parts of the temporal lobe. Our results also suggest that the combination of PET and MRI may facilitate the noninvasive diagnosis of MTLE.

Adult↗

Depth electrode studies in temporal lobe epilepsy: relation to quantitative magnetic resonance imaging and operative outcome.

We performed a retrospective study of 30 patients with presumed intractable temporal lobe epilepsy (TLE) who underwent chronic intracranial EEG monitoring (CIEM). Multicontact depth electrodes were stereotactically implanted through the medial occipital lobe into amygdala and hippocampus. All patients had previously undergone extracranial ictal EEG monitoring that proved inadequate to localize the epileptogenic zone. No morbidity was associated with CIEM in the 30 patients. Twenty-five patients were shown to have exclusively or predominantly unilateral temporal lobe seizures, and 5 patients had bitemporal seizures without unilateral predominance; 24 patients subsequently underwent an anterotemporal lobe cortical resection. Twenty-one patients have been followed a minimum of 1 year postoperatively. Nine patients (43%) had a class I outcome (seizure-free, auras only, or provoked seizures), 3 patients (14%) had a class II outcome (> or = 95% seizure reduction), 4 patients (19%) had a class III outcome (> or = 50% seizure reduction); and 5 patients (24%) had a class IV outcome (< 50% seizure reduction or no change). A prolonged interhemispheric propagation time (p < 0.01) and magnetic resonance imaging (MRI)-identified hippocampal atrophy (p < 0.01) correlated with a favorable surgical outcome. Results of this study may prove useful in counseling patients who undergo CIEM before temporal lobe surgery.

Adolescent↗

Regional distributions of hippocampal Na+,K(+)-ATPase, cytochrome oxidase, and total protein in temporal lobe epilepsy.

Na+,K(+)-ATPase (the sodium pump) is a ubiquitous enzyme that consumes ATP to maintain an adequate neuronal transmembrane electrical potential necessary for brain function and to dissipate ionic transients. Reductions in sodium pump function augment the sensitivity of neurons to glutamate, increasing excitability and neuronal damage in vitro. Temporal lobe epilepsy (TLE) is one disease characterized by hyperexcitability and marked hippocampal neuronal losses that could depend in part, on impaired sodium pump capacity secondary to changes in sodium pump levels and/or insufficient ATP supply. To assess whether abnormalities in the sodium pump occur in this disease, we used [3H]ouabain to determine the density of Na+,K(+)-ATPase for each anatomic region of hippocampus by in vitro autoradiography. Tissues were surgically obtained from epileptic patients with hippocampal sclerosis and compared with specimens from patients with seizures originating from temporal lobe tumors and autopsy controls. Changes in cellular population arising from neuronal losses or gliosis were assessed by protein densities derived from quantitative computerized densitometry of Coomassie-stained tissue sections. We estimated regional differences in capacity for ATP generation by determining cytochrome c oxidase (CO) activity. Principal neurons of hippocampus exhibit high levels of sodium pump enzyme. Both epilepsy groups exhibited slight but significant increases in sodium pump density/unit mass of protein in the dentate molecular layer, CA2, and subiculum as compared with autopsy controls. Greater hilar sodium pump density was also observed in sclerotic hippocampi. In contrast, CO activity was reduced in both epilepsy types throughout hippocampus. Results suggest that although sodium pump protein in surviving neurons appears to be upregulated in epilepsy, sodium pump capacity may be limited by the reduced levels of CO activity. Functional reduction in sodium pump capacity may be an important factor in hyperexcitability and neuronal death.

Autoradiography↗

Positron emission tomography with [11C]deuterium-deprenyl in temporal lobe epilepsy.

We performed positron emission tomography (PET) with [11C]deuterium-deprenyl in 9 patients with temporal lobe epilepsy (TLE) undergoing evaluation for possible epilepsy surgery. Seven patients had unilateral and 2 had bilateral mesiotemporal epileptic foci based on the preoperative investigation including ictal EEG discharges and PET with 2-[18F]fluoro-2-deoxyglucose (FDG). Deprenyl is an irreversible inhibitor of monoamine oxidase type B (MAO-B) with a very high affinity for the enzyme. In the brain, MAO-B is preferentially located in astrocytes, and a previous in vitro study showed increased binding of the ligand in sclerotic hippocampi. Dynamically acquired N-[methyl-11C]-a,a-di-deutero-L-deprenyl distribution in PET images were analyzed graphically, and the focus regions were assessed visually on the PET images. In addition, the accumulation rate and distribution volume of the tracer relative to the cerebellar cortex were measured in standardized homologous temporal regions by semiquantitative methods. Uptake of [11C]deuterium-deprenyl was significantly increased in the epileptogenic temporal lobes, both apparently and semiquantitatively. By calculating mean interlobar ratios, we identified the temporal lobe containing the epileptic focus in six unilateral cases. One case was ambiguous but was not falsely localized. The two bilateral cases were correctly identified as such. Our results suggest that PET with [11C]deuterium-deprenyl might be a useful method for identification of epileptogenic temporal lobes.

Adult↗

Chemosensory event-related potentials in patients with temporal lobe epilepsy.

We investigated chemosensory functions in patients with temporal lobe epilepsy (TLE) to discover whether olfactory and trigeminal stimuli applied either ipsilaterally or contralaterally to the epileptic focus are processed differently. Twenty-two patients were investigated, 12 of whom had epilepsy with a focus located in left temporal lobe (LTL). The remaining 10 patients had a right temporal lobe (RTL) focus. Input from the trigeminal system was examined by use of CO2; input from the olfactory system was evaluated with vanillin and hydrogen sulfide as stimuli. Chemosensory function was assessed by evaluation of chemosensory event-related potentials (CSERP) and the patients' verbal reports in an odor identification test. In both groups of patients, prolonged CSERP latencies were noted after stimulation of the left nostril with CO2 as compared with stimulation of the right nostril. In contrast, a different pattern emerged for olfactory stimuli. After right-sided olfactory stimulation, latencies were prolonged in patients with right-sided epileptical foci. Similarly, when the left nostril was stimulated in patients with a left-sided focus, CSERP latencies were prolonged. Thus, neocortical processing of olfactory, but not trigeminally mediated information evidently is affected by functional lesions of the temporal lobe. After olfactory stimulation in patients with a right-sided focus, the distribution of amplitudes was different from normal. Moreover, analyses showed nonoverlapping 95% confidence intervals (CI) for latency N1 when vanillin was applied to the right nostril. These results indicate that RTL may play a different role in processing of olfactory information as compared with LTL.

Adult↗

Physiologic and morphologic characteristics of granule cell circuitry in human epileptic hippocampus.

Morphological and electrophysiological techniques were used to examine granule cells and their mossy fiber axons in nine surgically resected hippocampal specimens from temporal lobe epilepsy (TLE) patients. Timm histochemistry showed mossy fiber sprouting into the inner molecular layer (IML) of the dentate in a subset of tissue samples. In slices from five tissue samples, stimulus-induced bursting activity could be induced with a low concentration (2.5 microM) of bicuculline; bursts were sensitive to the N-methyl-D-aspartate (NMDA) blocker, APV. There was a general correlation between such sprouting and experimentally induced hyperexcitability. Fourteen granule cells from five tissue samples were intracellularly stained [with lucifer yellow (LY) or neurobiotin]. Axons from a subset of these neurons showed axon collaterals reaching into the IML, but this axon projection pattern for single cells was not directly correlated with degree of mossy fiber sprouting shown grossly by Timm staining. Electron microscopic examination of intracellularly stained elements showed mossy fiber axon terminals making asymmetric synaptic contacts (including autapses on the granule cell dendrite) with dendritic shafts and spines in both apical and basal domains. These data are consistent with the hypothesis that mossy fiber sprouting provides a structural basis for recurrent excitation of granule cells, but does not provide direct support of the hypothesis that mossy fiber sprouting causes hyperexcitability. The data suggest that granule cell bursting activity is at least in part a function of compromised synaptic inhibition, since levels of gamma-aminobutyric acid (GABA) blockade that are generally subthreshold for burst induction were epileptogenic in some tissue samples from human epileptic hippocampus.

Action Potentials↗

Memory tests distinguish between patients with focal temporal and extratemporal lobe epilepsy.

We examined the ability of preoperative memory performance to distinguish between patients who had been diagnosed as having left (LTLE, n = 31), right (RTLE, n = 37), and extra-(ETLE, n = 17) temporal lobe focal epilepsy. All patients eventually underwent surgical resections. Analyses indicated that the ETLE group performed better than the RTLE group on nonverbal memory measures and better than the LTLE group on verbal memory measures. Discriminant function analyses indicated that use of a combination of measures that assess different aspects of memory were of significant value in distinguishing between patients with focal TLE and ETLE. This approach, as compared the use of single measures, improved classification rates of all three groups. The best single predictor of group membership, an index of verbal learning, yielded a 47% overall correct classification rate, with sensitivities ranging from 25 to 59%, and performed at worse than chance levels in classifying RTLE patients. A multivariate approach, which included an index of verbal and nonverbal learning, incidental nonverbal memory, and consolidation of organized and rote verbal material, yielded a 65% correct classification rate, with sensitivities ranging from 57 to 75%. This compares favorably with the other noninvasive techniques for lateralizing epileptogenic lesions.

Adolescent↗

Emanuel Swedenborg.

How is it that the name of a brilliant 18th century scientist and philosopher, many of whose exceptional achievements were often advanced for his time, is almost never mentioned in the annals of science? And how did it happen that a man very deeply dedicated to the advancement of science experienced a vision that completely altered the course of his life? We suggest, based on his extensive self-analytical writings, that the source of his spiritual experiences was temporal lobe epilepsy (TLE) and that he is among the group of creative religious thinkers also suspected or known to have had epilepsy, from St. Paul and Mohammed to Dostoevsky, who have changed Western civilization.

Epilepsy, Temporal Lobe↗

Cortical stimulation elicits regional distinctions in auditory and visual naming.

We used electrical stimulation mapping to compare performance on auditory and visual naming tasks in inferotemporal, lateral temporal, frontal, and parietal cortex in 8 temporal lobe epilepsy (TLE) patients with subdural electrodes placed for preoperative language localization. Performance on auditory responsive naming (ARN) and visual confrontation naming (VCN) was best during stimulation of parietal cortex and was equally impaired during stimulation of inferotemporal and frontal cortex. In contrast, ARN performance was significantly poorer than VCN performance during stimulation of anterior and posterior lateral temporal cortex. In most patients, stimulation of inferotemporal cortex at relatively low stimulus intensities (< or = 5 mA) during either ARN or VCN elicited reproducible errors in which patients could describe, gesture, spell, or draw, but not name, in response to auditory or visual cues. Inferotemporal and frontal cortex appear to be multimodality language regions distinct from lateral temporal cortex.

Adult↗